A clinical trial is a study following a pre-designed protocol to consider the effectiveness of a treatment for biomedical or health-related benefit in humans. Most clinical trials are either interventional or observational types of studies. In interventional studies, an investigator measures an outcome of an intervention, usually in the form of a treatment given to a group of subjects. In observational studies, an investigator would record what he or she observes from the subjects subjected to a study protocol.
In general, there are five different types of trials. Treatment trials test for the effectiveness of experimental treatments, such as new combinations of drugs, or new approaches to surgical or radiological method. On the other hand, prevention trials attempt to find better ways to prevent disease in people who have not experienced the disease. Another focus of a prevention trial is to prevent the disease from returning in subjects experienced with the disease. An exemplary approach is a vaccine trial. Prevention trials can use medicines, vitamins, minerals, or lifestyle changes. Diagnostic trials are studies designed to find more convenient, accurate, easily accessible, and rapid procedures for the diagnosis of a disease or condition. Screening trials focus on better ways to aid earlier and accurate detection of a disease or a health conditions. Lastly, quality of life trials, also called supportive care trials, inquire into ways to improve comfort and the quality of life for subject with a chronic disease.
A clinical protocol is a pre-designed, written guideline detailing the type, objective, and requirements (such as devices, supportive infrastructure, and subject characteristics) of a clinical trial, and the clinical trial endpoints. A clinical trial endpoint can include a state of a disease, a symptom, or a clinical sign that mirrors the target goal of a trial. In a typical setting, what are actually measured in a clinical trial are clinical trial endpoints. Combined results obtained from a variety of measured clinical trial endpoints are often evaluated in terms of their support of one or more clinical objectives or goals. The use of clinical trial endpoints such as tumor size, physiological data, vital signs associated with a state of healthiness or expression of well-being enable an investigator to quantitatively measure the effectiveness of a medical product to the stated goal of a trial. For example, chest pain can be used as a clinical trial endpoint in a clinical trial investigating the ability of a medical product to prevent a heart attack. When a subject is enrolled in the clinical trial and a medical product over a period of time, the subject can report back to an investigator any episodes of chest pain over the course of the trial. The number of subjects reporting chest pain and/or the number of incidences of chest pain in each subject can be quantified and expressed as a fraction to the entire population of subjects enrolled in the clinical trial. In some examples a medical product is administered to a first group of subjects and a placebo is administered to a second group of subjects. The results observed in the group of subjects administered a medical product can be compared to the results in the observed in the group of subjects administered a placebo- to determine if there is a causative relationship between the medical intervention and the clinical trial endpoint.
A surrogate endpoint is a measure of an effect of a certain treatment that can correlate with a clinical endpoint but does not necessarily have a guaranteed relationship. The National Institutes of Health defines a surrogate endpoint as a biomarker intended to substitute for a clinical endpoint. Surrogate markers are used when the primary endpoint is not desirable, such as death, or very difficult to attain and thus making it impractical to conduct a clinical trial to gather a statistically significant number of clinical endpoints. An example of a surrogate endpoint is the level of cholesterol in a clinical trial testing a medical product in a group of patients with cardiovascular disorder. While above normal cholesterol levels in a subject can increase the chances of a cardiovascular disorder, the relationship is not an absolute indicator of risk as some subjects with above normal levels of cholesterol do not develop cardiovascular disorder or show signs of heart disease.
Some clinical trial endpoints are qualitative and subjective indicators. In a clinical trial, subjective indications can be quantified by assigning numeric values to indicate the intensity of pain or experience. The measurement of a subjective indication is a difficult undertaking as it can be affected by subtle differences in the design of the clinical trial. For example, when a subject is posed the question “do you experience pain”, the answer can be markedly affected by the manner in which the question is presented. For example, when a person is given a range of scores to choose in response to a question of severity of pain, the answer provided can be affected by environmental cues, such as whether or not the question is presented on a graphical display or is asked by a person. Responses can also be affected by variables such as the color or size of a screen display. The characteristics of the person, such as gender, age, friendliness, profession (trained interviewer, psychiatrist, clinician, health care administrator, etc); presenting the question can also affect the answers provided. Other variables that can affect an answer include the time of the question, the room environment (closed, open), or whether a multiple choice or a numeric scale is used by a subject to select an answer.
A clinical trial endpoint can reliably predict the clinical outcome of a subject. Under some conditions, satisfying the clinical trial endpoint indicates that a desired outcome has been successfully reached. Multiple clinical trial endpoints in a trial can be combined to corroborate an indication that a clinical trial goal is met by a medical product. Careful clinical trial design allows the use of subjective indications, to be employed in a clinical trial to validate the goal of the trial.
In the past, subjective indications in a clinical setting have generally been recorded by clinicians or caregivers. However, the experiences recited by a subject is filtered and rephrased by the person administering the interview. Recently, the filtering was recognized as one of the factors contributing to the potential unreliability of subjective indications as clinical endpoints. Therefore, modern clinical trials have begun to develop better ways to produce more comprehensive pictures of subjective indications such as the status of a subject in terms of their symptoms and the impact of those symptoms on the subject's daily life.
Patient-reported outcome (PRO) is a measurement of an aspect of a subject's health status that comes directly from the subject (i.e., without the interpretation of the subject's responses by a physician or anyone else). A PRO instrument can be used to obtain a measurement by questionnaire, diary, or other forms of media allowing verbal or written expression of health status. In one embodiment, a health-related quality of life (HRQOL) questionnaire is a PRO instrument and is used to evaluate physical, social, psychological functioning of a subject.